Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide.
The pharmacokinetic parameters of morphine, morphine-6-glucuronide, and morphine-3-glucuronide were studied after single-dose morphine administration by five different routes. The quantitative significance of the active metabolite morphine-6-glucuronide was assessed, and the effects of novel dosing forms on morphine metabolism and distribution were examined. After administration of intravenous morphine the morphine-6-glucuronide plasma AUC exceeded that of morphine. After administration of oral morphine very low morphine levels were observed--the morphine-6-glucuronide plasma AUC exceeded that of morphine by a factor of 9:1. Sublingual, buccal, and sustained-release buccal morphine tablet administration resulted in delayed absorption, with attenuation and delay of peak morphine and metabolite levels. Morphine bioavailability and morphine glucuronide production were not altered.
Osborne
R
R
Imperial Cancer Research Fund Department of Medical Oncology, St. Bartholomew's Hospital, London, England.
Joel
S
S
Trew
D
D
Slevin
M
M
D000284:Administration, Oral; D000328:Adult; D003692:Delayed-Action Preparations; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D009022:Morphine Derivatives / Q000097:blood / Q000378:metabolism*; D013607:Tablets
D003692:Delayed-Action Preparations; D009022:Morphine Derivatives; D013607:Tablets; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide